Efficacy of Non-opioid Drugs in Addition to Opioid Therapy for Cancer Pain Management

Phase 3Not Yet RecruitingNCT07682558

University Hospital, Basel, Switzerland318 enrolled

Overview

The investigators investigate the efficacy of non-opioid analgesics compared to placebo together with opioid therapy for cancer pain management.

Pain in cancer is common and can be very debilitating. Approximately half of all people with a tumor experience moderate to severe pain during the course of patient's cancer. Nevertheless, pain management is often difficult because there are not yet enough reliable studies for some medications, especially when used in addition to opioids. Therefore, the NoDoubt study is investigating whether metamizole and/or ibuprofen - compared to a placebo - in addition to opioids provide better pain relief for cancer patients. The main goal is to reduce pain intensity. The study also examines whether the need for opioids can be reduced. The results could help to establish a clear and standardized practice for the treatment of cancer pain in the future, thus leading to improved care for cancer patients.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

318

Conditions

Cancer Pain Cancer Palliative Care

Interventions

MetamizoleDRUG

Metamizole 4 g/d as: 2 capsules of 500 mg Metamizole each (1000 mg) taken 4 x daily orally.

IbuprofenDRUG

Ibuprofen 1.2 g/d as: 2 capsules of 150 mg Ibuprofen each (300 mg) taken 4 x daily orally

PlaceboOTHER

Placebo 0 g/d as: 2 capsules containing inactive substance (mannitol) taken 4 x daily orally.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Inpatient setting (discharge possible, if patient returns for End of Study Visit) * Diagnosis of metastatic or locally advanced cancer * Cancer pain as defined by IASP (International Association for the Study of Pain) * Cancer pain therapy with opioids indicated for pain management or start thereof at baseline (drug, dose, and route at treating physician's discretion) * Average daily pain intensity ≥ 3 on NRS (Numeric Rating Scale) * Ability to swallow oral medication * Informed Consent as documented by signature Exclusion Criteria: * History of allergy or allergy-like symptoms (bronchospasm, urticaria or severe cutaneous adverse reactions (SCARs)) or hypersensitivity to dipyrone (or other pyrazolones or pyrazolidines) or ibuprofen (or other Non-steroidal anti-inflammatory drug incl. acetylsalicylic acid) * Moderate to severe renal insufficiency (creatinine-eGFR (estimated Glomerular Filtration Rate) \<45 ml/min) * Severe heart failure (New York Heart Association class III-IV) * Severe hepatic impairment (liver cirrhosis with ascites) or hepatic porphyria * History of agranulocytosis induced by dipyrone (or other pyrazolones or pyrazolidines) * Active gastric and/or duodenal ulcers or bleeding * History of recurrent gastric and/or duodenal ulcers or gastrointestinal bleeding (≥2 distinct episodes of proven ulceration or bleeding) or increased tendency to bleeding * Third trimester of pregnancy * Breastfeeding * G6PD deficiency * Inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis) * Intrathecal or epidural opioids or local or regional anesthetic therapy * Additional second opioid for co-analgesic effects or other reasons (e.g., methadone, buprenorphine) * Initiation of therapy with transdermal therapeutic system (TTS) opioid \<48 hours before start of IMP * Use of non-opioids with long half-life (i.e., acemetacin, celecoxib, etodolac, etoricoxib, ketorolac, naproxen, piroxicam, tenoxicam) * Pain unrelated to cancer (e.g. chronic non-cancer pain \[CNCP\], postoperative, particularly following coronary artery or cardiopulmonary bypass surgery) * Inability to follow study procedures or adhere to protocol (e.g., due to language problems, psychological disorders, dementia) * Inability to abstain from other non-opioids (apart from IMP (Investigational Medicinal Product)) during study participation * Participation in any interventional study targeted at pain management * Participant is a family member or employee of the investigator

Locations (1)

University Hospital Basel

Basel, Switzerland

Outcomes

Primary Outcomes

Change in cancer pain

The primary outcome will help to determine whether adding metamizole (dipyrone) or ibuprofen to opioids is more effective than adding placebo in reducing average daily pain intensity (primary outcome) in cancer patients. \- Average of 5-day average daily patient reported pain assessed on days 3 to 7 by numeric rating scale (NRS); The NRS ranges from 0 ("no pain") to 10 ("pain as bad as the patient can imagine")

Time frame: up to 5 days

Secondary Outcomes

Assessment of equivalence of metamizole and ibuprofen in analgesic potency regarding the pain intensity

Our main secondary outcome will help to investigate whether metamizole and ibuprofen demonstrate similar analgesic potency (are equivalent) regarding the pain intensity. For assessment of equivalence, Average of 5-day average daily patient reported pain assessed on days 3 to 7 by numeric rating scale will be used.

Time frame: up to 5 days

Worst pain in the past 24 hours by NRS

This outcome will be assessed at baseline and daily from day 3 to 7 using item 3 of the BPI-SF (Brief Pain Inventory - Short Form). The NRS ranges from 0 ("no pain") to 10 ("pain as bad as the patient can imagine"). It will also be assessed at End of Study Visit (EOS).

Time frame: up to 8 days

Least pain in the past 24 hours by NRS

This outcome will be assessed at baseline and daily from day 3 to 7 using item 4 of the BPI-SF. The NRS ranges from 0 ("no pain") to 10 ("pain as bad as the patient can imagine"). It will also be assessed at EOS.

Time frame: up to 8 days

Daily differences in pain intensity measured by NRS

This outcome will be assessed daily from day 3 to day 7 to investigate efficacy over the course of time. The NRS ranges from 0 ("no pain") to 10 ("pain as bad as the patient can imagine")

Central Contacts

Christopher Boehlke, Prof. Dr.

CONTACT

+41 61 265 25 25,christopher.boehlke@unibas.ch

Ursina Wernli, PhD

CONTACT

ursina.wernli@usb.ch

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.